Antiretroviral Therapy Reduces HIV Transmission in Discordant Heterosexual
Starting combination antiretroviral
therapy (ART) early -- at CD4 cell counts higher than
those recommended by global treatment guidelines -- led to
a decrease in HIV transmission between serodiscordant (one
positive, one negative) heterosexual couples in Africa, researchers
reported at the 17th Conference on Retroviruses and Opportunistic
Infections (CROI 2010) last month
in San Francisco. One case of transmission did occur from
a treated individual, however, indicating that ART does not
well known that effective combination ART can suppress HIV to a low
or undetectable level in the blood. Blood viral load typically (but
not always) correlates with levels in semen and female genital fluids,
suggesting that treatment could reduce the risk of sexual transmission.
models indicate that widespread early treatment of all people who test
HIV positive could dramatically reduce or even eliminate transmission,
and there is some early evidence that this may be happening in certain
populations; however, it has not been studied in formal clinical trials.
Deborah Donnell reported findings from a sub-study of the Partners in
Prevention trial, a large randomized study designed to assess whether
treating herpes simplex virus 2 (HSV-2), the usual cause of genital
herpes, could reduce HIV transmission. As
previously reported, the study found that daily acyclovir did not
reduce the likelihood of HIV transmission, even though it was associated
with lower plasma HIV viral load and fewer genital ulcers.
in Prevention also included a non-randomized observational component
looking at the effect of ART on HIV transmission.
The analysis included more than 3000 serodiscordant heterosexual couples
from 7 countries in sub-Saharan Africa (Botswana, Kenya, Rwanda, South
Africa, Tanzania, Uganda, and Zambia). The average ages were 29 for
women and 37 for men 37. In about two-thirds of the couples, the woman
was HIV positive and the man was initially negative. All HIV positive
partners also had HSV-2. At study entry, one-third of participants reported
having unprotected sex with their primary partner during the previous
The mean baseline CD4 count was about 400 cells/mm3. Trial eligibility
criteria required that none of the HIV positive partners have a CD4
cell count low enough to meet national criteria for starting ART (<250
cells/mm3), but they began therapy if their CD4 count fell to that threshold.
(When the trial began, global guidelines called for treatment when the
CD4 count fell bellow 200 cells/mm3, but this was recently
raised to 350 cells/mm3.
were followed for up to 24 months. HIV negative partners received HIV
tests every 3 months and HIV positive partners had their CD4 counts
measured every 6 months. If a person became infected, their virus was
genetically sequenced to ascertain whether it was the same as that of
their partner, in order to verify whether transmission occurred within
the study, 349 HIV positive participants (10%) started ART:
with < 200 cells/mm3;
with 200-349 cells/mm3;
with ? 350 cells/mm3 (about one-third for prevention of mother-to-child
higher proportion of men than women started therapy (12% vs 9%,
respectively), at median CD4 counts of 192 and 204 cells/mm3, respectively.
unprotected sex decreased after an HIV positive partner started
ART (from 6.2% to 3.7%), but frequency of sex remained stable.
total new infections occurred, of which 108 were verified as transmissions
within a couple; 5 were excluded because it was not known if the
partner was on ART or because the HIV positive partner was taking
drugs to prevent mother-to-child transmission.
cases of verified HIV transmission occurred from participants not
taking ART, for an incidence rate of 2.23 per 100 person-years.
1 verified transmission occurred from an individual while on ART,
for an incidence rate of 0.39 per 100 person-years.
relative risk of transmission from a partner on ART compared with
no ART (adjusted for CD4 count) was 0.08, or a 92% risk reduction
(although the single data point rendered the statistically analysis
not very robust).
the single HIV transmission after ART initiation, the HIV positive
partner had a CD4 count in the 200-350 cells/mm3 range and had initiated
ART 18 days prior to their partner's first seropositive test.
transmissions from people not on ART, partners with a CD4 count
< 200 cells/mm3 were about 5-fold more likely to transmit HIV
than those with > 350 cells/mm3:
200 cells/mm3: annual incidence rate 8.79;
cells/mm3: annual incidence rate 2.79;
cells/mm3: annual incidence rate 1.70;
500 cells/mm3: annual incidence rate 1.82.
on these findings, the investigators concluded, "This large prospective
study demonstrates that ART use is associated with substantially lower
risk for HIV transmission among heterosexual, African, HIV serodiscordant
couples, where the HIV-infected partner did not meet national criteria
for ART initiation at enrollment."
Noting that 1 transmission did occur while on ART, Donnell said that
serodiscordant couples should be advised to continue safer sex practices
even if the HIV positive partner starts treatment.
Fred Hutchinson Cancer Res Ctr, Seattle, WA; Univ of Nairobi and
Kenyatta Natl Hosp, Kenya; Univ of Washington, Seattle, WA; Univ of
California, San Francisco, CA.
Donnell, J Kiarie, K Thomas, and others. ART and Risk of Heterosexual
HIV-1 Transmission in HIV-1 Serodiscordant African Couples: A Multinational
Prospective Study. 17th Conference on Retroviruses & Opportunistic
Infections (CROI 2010). San Francisco. February 16-19, 2010. Abstract